LIVIVO - Search results -

Search results

Result 1 - 10 of total 14

Search options

Article: A novel variant of NR5A1, p.R350W implicates potential interactions with unknown co-factors or ligands.

Gau, Maki / Suga, Ryota / Hijikata, Atsushi / Kashimada, Ayako / Takagi, Masatoshi / Nakagawa, Ryuichi / Takasawa, Kei / Shirai, Tsuyoshi / Kashimada, Kenichi / Morio, Tomohiro

Frontiers in endocrinology

2023 Volume 13, Page(s) 1033074

Abstract: Introduction: NR5A1 and NR5A2 belong to an orphan nuclear receptor group, and approximately 60% of their amino acid sequences are conserved. Transcriptional regulation of NR5A receptors depends on interactions with co-factors or unidentified ligands.: ...

Abstract	Introduction: NR5A1 and NR5A2 belong to an orphan nuclear receptor group, and approximately 60% of their amino acid sequences are conserved. Transcriptional regulation of NR5A receptors depends on interactions with co-factors or unidentified ligands. Purpose and methods: We employed in vitro and in silico analysis for elucidating the pathophysiology of a novel variant in the ligand-binding domain of NR5A1, p.R350W which was identified from a 46,XY patient with atypical genitalia. Results: In the study, [1] reporter assays demonstrated that R350 is essential for NR5A1; [2] 3D model analysis predicted that R350 interacted with endogenous ligands or unknown cofactors rather than stabilizing the structure; [3] R350 is not conserved in NR5A2 but is specifically required for NR5A1; and [4] none of the 22 known missense variants of the ligand binding domain satisfied all the previous conditions [1]-[3], suggesting the unique role of R350 in NR5A1. Conclusion: Our data suggest that NR5A1 has unidentified endogenous ligands or co-activators that selectively potentiate the transcriptional function of NR5A1
MeSH term(s)	Humans ; Mutation ; Ligands ; Disorder of Sex Development, 46,XY ; Mutation, Missense ; Amino Acid Sequence ; Steroidogenic Factor 1/genetics
Chemical Substances	Ligands ; NR5A1 protein, human ; Steroidogenic Factor 1
Language	English
Publishing date	2023-01-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.1033074
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Initial patient choice of a growth hormone device improves child and adolescent adherence to and therapeutic effects of growth hormone replacement therapy.

Gau, Maki / Takasawa, Kei

Journal of pediatric endocrinology & metabolism : JPEM

2017 Volume 30, Issue 9, Page(s) 989–993

Abstract: Background: It is thought that growth hormone (GH) therapy success depends on the patient's adherence to their treatment regimen, but an optimal approach to improve adherence has not yet been established.: Methods: To evaluate the effect of patient ... ...

Abstract	Background: It is thought that growth hormone (GH) therapy success depends on the patient's adherence to their treatment regimen, but an optimal approach to improve adherence has not yet been established. Methods: To evaluate the effect of patient choice of a GH device on adherence to GH therapy, we carried out a retrospective longitudinal study of 46 GH deficient patients (24 boys, mean age of commencing GH therapy: 7.70±3.12 years) treated with recombinant GH therapy for 3 years, either with or without patient choice (n=28, 18, respectively). Results: The group comparison study for adherence, which evaluated the frequency of missed injections based on self-report, revealed that patient choice reduced the proportion of patients with low adherence 3 years after commencing GH therapy (33.3%-7.1%, p=0.042). Furthermore, this longitudinal study revealed that the patients with choice yielded significantly greater height standard deviation scores (SDS) (ΔHt SDS: 1.34±0.44 vs. 0.92±0.57, p=0.020) and insulin-like growth factor 1 (IGF-1) SDS (ΔIGF-1 SDS: 2.49±0.75 vs. 1.89±1.13, p=0.038) than those without choice. Conclusions: These results indicate that patient choice might improve adherence to GH therapy, which improves the therapeutic effects of GH therapy.
Language	English
Publishing date	2017-08-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1231070-0
ISSN	2191-0251 ; 0334-018X
ISSN (online)	2191-0251
ISSN	0334-018X
DOI	10.1515/jpem-2017-0146
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2258: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Phenotypic Variation in 46,XX Disorders of Sex Development due to the Fourth Zinc Finger Domain Variant of WT1: A Familial Case Report.

Kirino, Shizuka / Yogi, Analia / Adachi, Eriko / Nakatani, Hisae / Gau, Maki / Iemura, Ryosei / Yamano, Haruki / Kanamori, Toru / Mori, Takayasu / Sohara, Eisei / Uchida, Shinichi / Okamoto, Kentaro / Udagawa, Tomohiro / Takasawa, Kei / Morio, Tomohiro / Kashimada, Kenichi

Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation

2023 Volume 17, Issue 1, Page(s) 51–55

Abstract: Introduction: The variants in the zinc finger (ZF) domains 1-3 in WT1 are one of the major causes of 46,XY disorders of sex development (DSD). Recently, variants in the fourth ZF (ZF4 variants) were reported to cause 46,XX DSD. However, all the 9 ... ...

Abstract	Introduction: The variants in the zinc finger (ZF) domains 1-3 in WT1 are one of the major causes of 46,XY disorders of sex development (DSD). Recently, variants in the fourth ZF (ZF4 variants) were reported to cause 46,XX DSD. However, all the 9 patients reported were de novo, and no familial cases were identified. Case presentation and results: The proband (16-year-old social female) had a 46,XX karyotype with dysplastic testes and moderate virilization in genitalia. A ZF4 variant, p.Arg495Gln, in WT1 was identified in the proband, her brother, and mother. The mother did not show any virilization with normal fertility, and the 46,XY brother developed normal puberty. Conclusion: The phenotypic variations due to the ZF4 variant are extremely broad in 46,XX cases.
MeSH term(s)	Humans ; Male ; Female ; Adolescent ; Zinc Fingers/genetics ; Virilism ; Genitalia ; Biological Variation, Population ; 46, XX Disorders of Sex Development/genetics ; 46, XX Disorders of Sex Development/pathology ; Disorders of Sex Development/genetics ; WT1 Proteins
Chemical Substances	WT1 protein, human ; WT1 Proteins
Language	English
Publishing date	2023-02-16
Publishing country	Switzerland
Document type	Case Reports ; News
ZDB-ID	2253672-3
ISSN	1661-5433 ; 1661-5425
ISSN (online)	1661-5433
ISSN	1661-5425
DOI	10.1159/000529720
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 6595: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: BMP2 is a potential causative gene for isolated dextrocardia situs solitus.

Yogi, Analia / Iemura, Ryosei / Nakatani, Hisae / Takasawa, Kei / Gau, Maki / Yamauchi, Takeru / Yoshida, Masayuki / Moriyama, Keiji / Ishii, Taku / Hosokawa, Susumu / Yamada, Mamiko / Suzuki, Hisato / Kosaki, Kenjiro / Kashimada, Kenichi / Morio, Tomohiro

European journal of medical genetics

2023 Volume 66, Issue 9, Page(s) 104820

Abstract: BMP2 (bone morphogenic protein-2) is a member of the TGF-β superfamily and has essential roles in the development of multiple organs, including osteogenesis. Because of its crucial role in organ and skeletal development, Bmp2 null mice is fetal lethal. ... ...

Abstract	BMP2 (bone morphogenic protein-2) is a member of the TGF-β superfamily and has essential roles in the development of multiple organs, including osteogenesis. Because of its crucial role in organ and skeletal development, Bmp2 null mice is fetal lethal. The recent report has characterized multiple patients with BMP2 haploinsufficiency, describing individuals with BMP2 sequence variants and deletions associated with short stature without endocrinological abnormalities, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease. However, due to a small number of reported patients with BMP2 haploinsufficiency, the genotype and phenotype correlations are not fully understood. We experienced a family of BMP2 haploinsufficiency with a novel frameshift variant NM_001200.4: c.231dup (p.Tyr78Leufs*38) which was predicted to be "pathogenic" by the American College of Genetics and Genomics (ACGM) criteria. In addition to short stature, impaired hearing ability and minor skeletal deformities, the proband exhibited isolated dextrocardia situs solitus without cardiac anomalies and abnormal locations of other visceral organs. Our study would shed light on the crucial role of BMP2 in determining the cardiac axis, and further studies are needed to assemble more cases to elucidate BMP2 role in human heart development.
MeSH term(s)	Mice ; Animals ; Humans ; Dextrocardia/diagnostic imaging ; Dextrocardia/genetics ; Heart Defects, Congenital/genetics ; Genotype ; Family ; Dwarfism ; Transforming Growth Factor beta/genetics ; Bone Morphogenetic Protein 2/genetics
Chemical Substances	Transforming Growth Factor beta ; BMP2 protein, human ; Bone Morphogenetic Protein 2
Language	English
Publishing date	2023-08-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2184135-4
ISSN	1878-0849 ; 1769-7212
ISSN (online)	1878-0849
ISSN	1769-7212
DOI	10.1016/j.ejmg.2023.104820
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 84/9: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: A MinION-based Long-Read Sequencing Application With One-Step PCR for the Genetic Diagnosis of 21-Hydroxylase Deficiency.

Adachi, Eriko / Nakagawa, Ryuichi / Tsuji-Hosokawa, Atsumi / Gau, Maki / Kirino, Shizuka / Yogi, Analia / Nakatani, Hisae / Takasawa, Kei / Yamaguchi, Tomomi / Kosho, Tomoki / Murakami, Masanori / Tajima, Toshihiro / Hasegawa, Tomonobu / Yamada, Tetsuya / Morio, Tomohiro / Ohara, Osamu / Kashimada, Kenichi

The Journal of clinical endocrinology and metabolism

2023 Volume 109, Issue 3, Page(s) 750–760

Abstract: Context: Recently developed long-read sequencing (LRS) technology has been considered an option for CYP21A2 analysis. However, the clinical use of LRS for CYP21A2 analysis is limited.: Objective: This study's objective is to develop an efficient and ... ...

Abstract	Context: Recently developed long-read sequencing (LRS) technology has been considered an option for CYP21A2 analysis. However, the clinical use of LRS for CYP21A2 analysis is limited. Objective: This study's objective is to develop an efficient and low-cost LRS system for CYP21A2 screening. Methods: A DNA fragment library was prepared in a single polymerase chain reaction (PCR) that covers the entire CYP21A2 gene and all known junctions caused by TNXB gene structural rearrangements, yielding a single 8-kb product of CYP21A2 or CYP21A1P/CYP21A2 chimera. After barcoding, the PCR products were sequenced on a MinION-based platform with Flongle Flow Cell R9.4.1 and R10.4.1. Results: The reference genotypes of 55 patients with 21-hydroxylase deficiency (21OHD) were established using the conventional method with multiplex ligation-dependent probe amplification (MLPA) and nested PCR. LRS using Flongle Flow Cell R9.4.1 yielded consistent results. Additionally, the recently updated LRS "duplex" analysis with Flongle flow cell R10.4.1 was tested to reveal an advantage of accurately sequencing a variant located on the homopolymer region. By introducing a barcode system, the cost was reduced to be comparable to that of conventional analysis. A novel single-nucleotide variation was discovered at the acceptor site of intron 7, c.940-1G > C. We also identified a subtype of the classical chimeric junction CH2, "CH2a," in the region from the latter part of intron 5 to exon 6. Conclusion: We successfully established a novel low-cost and highly accurate LRS system for 21OHD genetic analysis. Our study provides insight into the feasibility of LRS for diagnosing 21OHD and other genetic diseases caused by structural rearrangements.
MeSH term(s)	Humans ; Steroid 21-Hydroxylase/genetics ; Adrenal Hyperplasia, Congenital/diagnosis ; Adrenal Hyperplasia, Congenital/genetics ; Genotype ; Multiplex Polymerase Chain Reaction ; Mutation
Chemical Substances	Steroid 21-Hydroxylase (EC 1.14.14.16) ; CYP21A2 protein, human (EC 1.14.14.16)
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad577
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.134: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Clinical report: Chronic liver dysfunction in an individual with an AMOTL1 variant.

Kirino, Shizuka / Suzuki, Mitsuyoshi / Ogawa, Takuya / Takasawa, Kei / Adachi, Eriko / Gau, Maki / Takahashi, Ken / Ikeno, Mitsuru / Yamada, Mamiko / Suzuki, Hisato / Kosaki, Kenjiro / Moriyama, Keiji / Yoshida, Masayuki / Morio, Tomohiro / Kashimada, Kenichi

European journal of medical genetics

2022 Volume 65, Issue 11, Page(s) 104623

Abstract: AMOTL1 is a member of the Motin protein family and localizes to tight junctions and is involved in cell polarity and paracellular permeability. Pathological variants have been reported in three patients from two separate families in recent years. The ... ...

Abstract	AMOTL1 is a member of the Motin protein family and localizes to tight junctions and is involved in cell polarity and paracellular permeability. Pathological variants have been reported in three patients from two separate families in recent years. The clinical spectrum includes cleft lip and palate along with a high incidence of congenital cardiac disease and ear malformations. We report a case of AMOTL1 pathogenic variant in a 11-year-old male patient with nonspecific and chronic liver dysfunction accompanied by persistently elevated liver enzymes since early infancy. Liver biopsy at 8 years of age revealed a mildly dilated central vein and sinusoid with no specific etiology. Liver dysfunction is not a known clinical feature of AMOTL1 malfunction. However, given that the protein is known to be involved in angiogenesis, it may be inferred that abnormalities in this process may lead to liver dysfunction. This is the first report of liver dysfunction identified in a patient with AMOTL1 malfunction, which will shed light on other putative functions of the protein.
MeSH term(s)	Angiomotins ; Child ; Cleft Lip/complications ; Cleft Palate/complications ; Humans ; Liver Diseases/genetics ; Male ; Membrane Proteins/metabolism
Chemical Substances	AMOTL1 protein, human ; Angiomotins ; Membrane Proteins
Language	English
Publishing date	2022-09-15
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	2184135-4
ISSN	1878-0849 ; 1769-7212
ISSN (online)	1878-0849
ISSN	1769-7212
DOI	10.1016/j.ejmg.2022.104623
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 84/9: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: The High Relevance of 21-Deoxycortisol, (Androstenedione + 17α-Hydroxyprogesterone)/Cortisol, and 11-Deoxycortisol/17α-Hydroxyprogesterone for Newborn Screening of 21-Hydroxylase Deficiency.

Watanabe, Kazuhiro / Tsuji-Hosokawa, Atsumi / Hashimoto, Atsuko / Konishi, Kaoru / Ishige, Nobuyuki / Yajima, Harumi / Sutani, Akito / Nakatani, Hisae / Gau, Maki / Takasawa, Kei / Tajima, Toshihiro / Hasegawa, Tomonobu / Morio, Tomohiro / Kashimada, Kenichi

The Journal of clinical endocrinology and metabolism

2022 Volume 107, Issue 12, Page(s) 3341–3352

Abstract: Context: There are limited reports on the detailed examination of steroid profiles for setting algorithms for 21-hydroxylase deficiency (21OHD) screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS).: Objective: We aimed to define an ... ...

Abstract	Context: There are limited reports on the detailed examination of steroid profiles for setting algorithms for 21-hydroxylase deficiency (21OHD) screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Objective: We aimed to define an algorithm for newborn screening of 21OHD by LC-MS/MS, measuring a total of 2077 dried blood spot samples in Tokyo. Methods: Five steroids (17α-hydroxyprogesterone [17αOHP], 21-deoxycortisol [21DOF], 11-deoxycortisol [11DOF], androstenedione [4AD], and cortisol [F]) were included in the panel of LC-MS/MS. Samples from 2 cohorts were assayed: Cohort A, 63 "screening positive" neonates who were referred to an endocrinologist (n = 26 with 21OHD; n = 37 false-positive; obtained from 2015 to 2020); and Cohort B, samples (n = 2014) with 17αOHP values in the 97th percentile or above, in the first-tier test with 17αOHP ELISA from 2020 to 2021. Results: Analysis of Cohort A revealed that the 3 indexes 21DOF, 11DOF/17αOHP, and (4AD + 17αOHP)/F had higher area under the curve (AUC) values (0.999, 0.997, 0.989, respectively), while the 17αOHP AUC was lower (0.970). Accordingly, in addition to 17αOHP, the 3 markers were included for defining the screening algorithm. The assay of Cohort B revealed that the new algorithm gave 92% of predicted positive predictive value without false-negative cases. We also determined the reference values for the 5 steroids at 4 to 7 days after birth, according to sex and gestational age (GA), revealing extremely low levels of 21DOF at any GA irrespective of sex differences. Conclusion: Our study demonstrated the high relevance of 21DOF, (4AD + 17αOHP)/F, and 11DOF/17αOHP, rather than 17αOHP, for 21OHD screening.
MeSH term(s)	Infant, Newborn ; Female ; Humans ; Male ; Cortodoxone ; Androstenedione ; Hydrocortisone ; Chromatography, Liquid/methods ; Neonatal Screening/methods ; Tandem Mass Spectrometry/methods ; 17-alpha-Hydroxyprogesterone ; Adrenal Hyperplasia, Congenital/diagnosis ; Steroids ; Androgens ; Endocrine System Diseases
Chemical Substances	21-deoxycortisol (641-77-0) ; Cortodoxone (WDT5SLP0HQ) ; Androstenedione (409J2J96VR) ; Hydrocortisone (WI4X0X7BPJ) ; 17-alpha-Hydroxyprogesterone (68-96-2) ; Steroids ; Androgens
Language	English
Publishing date	2022-09-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgac521
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.134: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Adrenal suppression and anthropometric data at two years of age was not influenced by the initial hydrocortisone dose in patients with 21-hydroxylase deficiency.

Saito, Yoko / Takasawa, Kei / Gau, Maki / Yamauchi, Takeru / Nakagawa, Ryuichi / Miyakawa, Yuichi / Sutani, Akito / Hosokawa-Tsuji, Atsumi / Takishima, Shigeru / Matsubara, Yohei / Morio, Tomohiro / Kashimada, Kenichi

Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology

2021 Volume 30, Issue 4, Page(s) 155–161

Abstract: In contrast to the glucocorticoid maintenance therapy employed in patients with 21 hydroxylase deficiency (21OHD), the initial therapy remains to be optimized. The Japanese Society for Pediatric Endocrinology recommends a hydrocortisone (HC) dose of 25- ... ...

Abstract	In contrast to the glucocorticoid maintenance therapy employed in patients with 21 hydroxylase deficiency (21OHD), the initial therapy remains to be optimized. The Japanese Society for Pediatric Endocrinology recommends a hydrocortisone (HC) dose of 25-100 mg/m
Language	English
Publishing date	2021-10-01
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2079760-6
ISSN	0918-5739
ISSN	0918-5739
DOI	10.1297/cpe.30.155
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5710: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Marked clinical heterogeneity in congenital hyperinsulinism due to a novel homozygous ABCC8 mutation.

Takasawa, Kei / Miyakawa, Yuichi / Saito, Yoko / Adachi, Eriko / Shidei, Tsunanori / Sutani, Akito / Gau, Maki / Nakagawa, Ryuichi / Taki, Atsuko / Kashimada, Kenichi / Morio, Tomohiro

Clinical endocrinology

2021 Volume 94, Issue 6, Page(s) 940–948

Abstract: Background: The most severe forms of congenital hyperinsulinism (CHI) are caused by inactivating mutations of two KATP channel genes, KCNJ11 and ABCC8. Unresponsiveness to diazoxide and need for subtotal pancreatectomy can usually be predicted by ... ...

Abstract	Background: The most severe forms of congenital hyperinsulinism (CHI) are caused by inactivating mutations of two KATP channel genes, KCNJ11 and ABCC8. Unresponsiveness to diazoxide and need for subtotal pancreatectomy can usually be predicted by genetic form, particularly biallelic mutations in KATP channel genes. A few reports indicated marked clinical heterogeneity in siblings with identical biallelic mutations in ABCC8. The clinical heterogeneity in biallelic KATP CHI was speculated to be caused by epigenetic and environmental factors or related to differences in splicing factor machinery. Objective: To elucidate the clinical pathophysiology, especially heterogeneity, among three cases with CHI caused by a homogenous novel mutation. Patients and methods: We report a case series that includes two siblings and one unrelated individual with CHI caused by a homogenous 1-bp deletion around the splice acceptor site at the exon 35 mutation of ABCC8, which exhibited markedly distinct phenotypes. To assess the effect of the mutation on splicing, we performed digital droplet polymerase chain reaction (ddPCR) on normal pancreas tissue and a patient's lymphocytes. Results: ddPCR of ABCC8 cDNA revealed that expression of exon 35 and its upstream and downstream regions did not differ. These data suggested that clinical heterogeneity may not be caused by differences in splicing factor machinery. Conclusion: The phenotypic variation in homozygotes could not be explained by splicing abnormalities. Though early genetic diagnosis of KATP CHI could contribute to selecting appropriate therapeutic options, more deliberate selection of therapeutic options in diffuse CHI due to biallelic ABCC8 mutations may be required.
MeSH term(s)	Biological Variation, Population ; Congenital Hyperinsulinism/genetics ; Diazoxide ; Humans ; Mutation ; Sulfonylurea Receptors/genetics
Chemical Substances	ABCC8 protein, human ; Sulfonylurea Receptors ; Diazoxide (O5CB12L4FN)
Language	English
Publishing date	2021-03-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	121745-8
ISSN	1365-2265 ; 0300-0664
ISSN (online)	1365-2265
ISSN	0300-0664
DOI	10.1111/cen.14443
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 814: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Two ovarian candidate enhancers, identified by time series enhancer RNA analyses, harbor rare genetic variations identified in ovarian insufficiency.

Human molecular genetics

2022 Volume 31, Issue 13, Page(s) 2223–2235

Abstract: The genetic regulation of ovarian development remains largely unclear. Indeed, in most cases of impaired ovarian development-such as 46,XX disorders of sex development (DSD) without SRY, and premature ovarian insufficiency (POI)-the genetic causes have ... ...

Abstract	The genetic regulation of ovarian development remains largely unclear. Indeed, in most cases of impaired ovarian development-such as 46,XX disorders of sex development (DSD) without SRY, and premature ovarian insufficiency (POI)-the genetic causes have not been identified, and the vast majority of disease-associated sequence variants could lie within non-coding regulatory sequences. In this study, we aimed to identify enhancers of five ovarian genes known to play key roles in early ovarian development, basing our analysis on the expression of enhancer derived transcripts (eRNAs), which are considered to characterize active enhancers. Temporal expression profile changes in mouse WT1-positive ovarian cells were obtained from cap analysis of gene expression at E13.5, E16.5 and P0. We compared the chronological expression profiles of ovarian-specific eRNA with expression profiles for each of the ovarian-specific genes, yielding two candidate sequences for enhancers of Wnt4 and Rspo1. Both sequences are conserved between mouse and human, and we confirmed their enhancer activities using transient expression assays in murine granulosa cells. Furthermore, by sequencing the region in patients with impaired ovarian development in 24 patients, such as POI, gonadal dysgenesis and 46,XX DSD, we identified rare single nucleotide variants in both sequences. Our results demonstrate that combined analysis of the temporal expression profiles of eRNA and mRNA of target genes presents a powerful tool for locating cis-element enhancers, and a means of identifying disease-associated sequence variants that lie within non-coding regulatory sequences, thus advancing an important unmet need in forward human genetics.
MeSH term(s)	Animals ; Enhancer Elements, Genetic/genetics ; Female ; Genetic Variation ; Humans ; Menopause, Premature/genetics ; Mice ; Primary Ovarian Insufficiency/genetics ; Primary Ovarian Insufficiency/metabolism ; RNA/genetics ; Time Factors
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2022-02-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddac023
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3469: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito